Process for preparation of 1,3-dioxolane-4-methanol compounds

ABSTRACT

A process for preparing easily and economically a 1,3-dioxolane-4-methanol compound in a racemic form or an optically active form with high purity and in high yield. 
     The process comprises reacting an alkali metal or alkaline earth metal salt of an alcohol or a carboxylic acid with a halogenomethyl-1,3-dioxolane which is prepared by acetalizing a halogeno-1,2-propanediol of a formula (1) wherein X is a halogen atom, in an acid catalyst to conduct esterification or etherification, and then hydrolyzing the ester group and hydrogenolyzing the ether group to prepare a 1,3-dioxolane-4-methanol compound of a formula (5) wherein R 1  and R 2  are hydrogen atom, alkyl having 1 to 4 carbon atoms or phenyl, and R 1  and R 2  may form a cycloalkyl ring having 3 to 6 carbon atoms with the adjacent carbon atoms. ##STR1##

This application is a 371 of PCT/JP97/03165 filed Sep. 9, 1997.

TECHNICAL FIELD

The present invention relates to a process for preparation of1,3-dioxolane-4-methanol compounds useful as an intermediate ofmedicines, agricultural chemicals, etc.

BACKGROUND ART

1,3-Dioxolane-4-methanol compounds are used as an intermediate ofmedicines, agricultural chemicals, etc. and following processes forpreparation of them are known: (i) A process for preparation of them byreacting glycerin and an acetonide reagent (Synth. Commun., 22,2653(1992), (ii) a process for preparation of them from mannitol(Biochem. Prep., 2, 31(1952)), (iii) a process for preparation of themfrom an ascorbic acid (J. Am. Chem. Soc., 102, 6304(1980), (iv) aprocess for preparation of them from serine (Japanese Patent PublicationB No. 6-62492), (v) an optical resolution of them by using an enzyme (J.Chem. Soc., Perkin Trans. I 23, 3459(1994) and so on.

These processes, however, have industrially following disadvantages:

According to the process for preparation of them by reacting glycerinand an acetonide reagent of (i), a mixture of a compound acetalizedbetween positions 1 and 2 and a compound acetalized between positions 1and 3 is produced and it is hardly difficult to separate each compoundfrom the mixture. According to the method of (ii), because chemicallyequivalent amount of lead tetraacetate or sodium periodic acid is usedin case of cleavage of 1,2-diol compounds, it takes high costs and incase of preparing an optical isomer, only a (S)-form is obtained becauseonly D-mannitol is present in nature. According to the process forpreparation of them from L-ascorbic acid or D-isoascorbic acid of (iii),because chemically equivalent amount of lead tetraacetate or sodiumperiodic acid is used, it takes high costs like in case of (ii).According to the method from serine of (iv), in case of preparing anoptical isomer, only a (R)-form is obtained because only a (L)-form ispresent in nature like in case of (ii) and furthermore in case ofreduction of the carboxylic acid, the reagent which is difficult to bedealt with in mass production such as lithium aluminum hydride etc. mustbe used. According to the process by the biochemically opticalresolution method of (v), purity of one of optical isomers is high, butpurity of the other is low, and in some cases, in order to separate anoptically active alcohol and an optically active ester which areprepared from a racemic alcohol, separation by column chromatography isnecessary and therefore, it is not suitable for mass production.Furthermore, any process mentioned above contains many steps and is notpractical. Therefore, a more efficient process for preparation of a1,3-dioxolane-4-methanol was desired.

DISCLOSURE OF INVENTION

The present inventors engaged extensively in solving above problems, andfound a novel process for preparing the above objective compound from a3-halogeno-1,2-propanediol.

The present invention relates to a process for preparing a1,3-dioxolane-4-methanol compound of the formula ##STR2## wherein R¹ andR² are the same or different and are hydrogen atom, alkyl having 1 to 4carbon atoms or phenyl, and R¹ and R² may form a cycloalkyl ring having3 to 6 carbon atoms with the adjacent carbon atoms, which ischaracterized in acetalizing a 3-halogeno-1,2-propanediol of the formula##STR3## wherein X is halogen atom, with an acetalizing agent in thepresence of an acid catalyst to prepare a 4-halogenomethyl-1,3-dioxolaneof the formula ##STR4## wherein R¹, R² and X are as defined above, andreacting it with an alkali metal salt or alkaline earth metal salt of acarboxylic acid or an alcohol of the formula

    ROH                                                        (3)

wherein R is acyl, aralkyl or allyl, to prepare a compound of theformula ##STR5## wherein R, R¹ and R² are as defined above, and when Ris acyl in the formula (4), subjecting it to hydrolysis, and when R isaralkyl or allyl in the formula (4) subjecting it to hydrogenolysis inthe presence of a reduction catalyst.

According to the present invention, in case of using an optically active3-halogeno-1,2-propanediol as a starting material, there is obtained anoptically active 1,3-dioxolane-4-methanol compound.

BEST MODE FOR CARRYING OUT THE INVENTION

The reaction of the present invention is schematically shown as follows.##STR6## in the above formulae X, R¹, R² and R are as defined above.

Each step is explained in detail as follows.

Step(A)

A 4-halogenomethyl-1,3-dioxolane of the formula (2) is obtained byreacting a 3-halogeno-1,2-propanediol of the formula (1) with anacetalizing agent in the presence of an acid catalyst.

Preferable examples of the 3-halogeno-1,2-propanediols are3-chloro-1,2-propanediol and 3-bromo-1,2-propanediol.

Examples of the acetalizing agents are ketones, such as acetone, diethylketone, benzophenone, cyclohexanone, etc., aldehydes, such asformaldehyde, acetoaldehyde, benzaldehyde, etc., dialkoxyacetals ofketones, such as 2,2-dimethoxypropane, 2,2-dimethoxypentane, etc., enolethers of ketones, such as 2-methoxypropene etc. and so on.

For instances, when a compound of the formula (2) wherein R¹ and R² arehydrogen atom is prepared, formaldehyde is used, when a compound of theformula (2) wherein R¹ and R² are phenyl, benzophenone is used, when acompound of the formula (2) wherein R¹ and R² form a 6 membered ringtogether with the adjacent carbon atoms is prepared, cyclohexanone isused, and when a compound of the formula (2) wherein R¹ is phenyl and R²is hydrogen is prepared, benzaldehyde is used.

When a 1,3-dioxolane-4-methanol of the formula (5) wherein R¹ and R² aremethyl is prepared, acetone, 2,2-dimethoxypropane and 2-methoxypropeneare especially preferable as an acetalizing agent.

The examples of the acid catalysts are organic acids, such asp-toluenesulfonic acid, pyridinium p-toluenesulfonate, camphorsulfonicacid, etc., mineral acids such as hydrochloric acid, sulfuric acid,phosphoric acid, etc., and Lewis acid, such as, trifluoroborate etc. Theamount of the acid catalyst is 0.05 to 0.1 mol equivalent to a3-halogeno-1,2-propanediol.

The examples of solvents are ethers, such as diethyl ether,tetrahydrofuran, 1,4-dioxane, etc., halogen compounds, such asdichloromethane, dichloroethane, etc., acetone and so on.

The reaction temperature is from 0° C. to refluxing temperature of thesolvent.

Step(B) (B-1) A 4-acyloxymethyl-1,3-dioxolane of the formula (4) inwhich R is acyl, is prepared by reacting a4-halogenomethyl-1,3-dioxolane of the formula (2) which is prepared bystep (A) with an alkali metal salt or alkaline earth metal salt of acarboxylic acid.

The examples of solvents are polar aprotic solvents, such asN,N-dimethylformamide, dimethyl sulfoxide etc., esters, such as ethylacetate, butyl acetate, etc., ethers, such as tetrahydrofuran,1,4-dioxane, 1,2-dimethoxyethane, diglyme, triglyme, diethlene glycolmonomethyl ether, etc., ketones, such as acetone, methyl ethyl ketone,methyl isobutyl ketone, etc., nitriles, such as acetonitrile etc.,halogen compounds, such as dichloromethane, 1,2-dichloroethane, etc.,water and a mixture of these solvents.

Examples of the alkali metal salts or alkaline earth metal salts of acarboxylic acid are salts of an aliphatic carboxylic acid having 1 to 4carbon atoms, salts of an aromatic carboxylic acid substituted orunsubstituted by an alkyl having 1 to 4 carbon atoms, nitro, cyano, ahalogen atom, or an alkoxy having 1 to 4 hydrocarbon. Preferable thecarboxylates are alkali metal salts or alkaline earth metal salts ofbenzoic acid and acetic acid, such as sodium benzoate, potassiumbenzoate, sodium acetate, potassium acetate, calcium benzoate, bariumbenzoate, etc.

The amount of the alkali metal salt or alkaline earth metal salt of acarboxylic acid is 1 to 3 moles per one mole of a4-halogenomethyl-1,3-dioxolane, preferably 1 to 2 moles. To use it inexcess does not affect the yield of the product, but it is noteconomical.

(B-2) A 4-alkoxymethyl-1,3-dioxolane of the formula (4) in which R isaralkyl or allyl, is prepared by reacting a4-halogenomethyl-1,3-dioxolane of the formula (2) which is prepared bystep (A) with an alkali metal salt or alkaline earth metal salt of analcohol.

Examples of the alcohols are ones having aralkyl group or allyl group,especially preferably benzyl alcohol and allyl alcohol. The amount ofthe alcohol is 1 to 4 mole equivalent to a4-halogenomethyl-1,3-dioxolane.

Examples of bases used in preparing the alkali metal salt or alkalineearth metal salt of an alcohol are alkali metal or alkaline earth metalcarbonates, such as sodium carbonate, potassium carbonate, calciumcarbonate, etc., alkali metal or alkaline earth metal hydroxides, suchas sodium hydroxide, potassium hydroxide, calcium hydroxide, bariumhydroxide, etc., alkali metal or alkaline earth metal hydrides, such assodium hydride, lithium hydride, calcium hydride, etc., preferablyalkali metal or alkaline earth metal hydroxides, such as sodiumhydroxide, potassium hydroxide, calcium hydroxide, alkali metal oralkaline earth metal hydrides, such as sodium hydride, lithium hydrideand calcium hydride.

Examples of solvents are polar aprotic solvents, such asN,N-dimethylformamide, dimethyl sulfoxide, etc., ethers such astetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, etc., halogencompounds, such as dichloromethane, 1,2-dichloroethane, etc., water anda mixture of these solvents. The alcohols used as a starting materialmay serve as a solvent by using in excess.

The reactions in steps (B-1) and (B-2) proceed without catalyst, but thereactions are accelerated by adding iodo compounds, such as cesiumiodide, sodium iodide, potassium iodide, etc., bromo compounds such ascesium bromide, sodium bromide, potassium bromide, etc., quaternaryammonium phase transfer salts such as terabutylammonium chloride,trimethylammonium bromide, etc., crown ether such as 18-Crown-6 etc.,especially effective in case of a halogen atom in the formula (2) beingchlorine atom. The preferable reaction promoters are an alkali metalbromide and an alkali metal iodide, especially sodium bromide, potassiumbromide, sodium iodide and potassium iodide. Its amount is 0.05 to 1.1mole equivalent to a 4-halogenomethyl-1,3-dioxolane. The reaction ratedecreases in less than the amount and it is not practical.

Step (C)

A 1,3-dioxolane-4-methanol compound of the formula (5) is obtained byhydrolysis of a 4-acyloxymethyl-1,3-dioxolane of the formula (4)prepared by the above step (B-1) with a base in a solvent.

Examples of the solvents are alcohols such as methanol, ethanol,propanol, butanol, etc., ethers such as tetrahydrofuran, 1,4-dioxane,1,2-dimethoxyethane, etc., water and a mixture of these solvents.

Examples of bases are alkali metal or alkaline earth metal carbonates,such as sodium carbonate, potassium carbonate, calcium carbonate, etc.,alkali metal or alkaline earth metal hydroxides, such as sodiumhydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide,etc. The amount of the base is 1 to 3 mole equivalent to a4-acyloxymethyl-1,3-dioxolane, preferably 1 to 1.5 mole equivalent. Thereaction temperature is from 0° C. to refluxing temperature of thesolvent.

A 1,3-dioxolane-4-methanol compound is obtained by catalytichydrogenolysis of an 4-alkoxymethyl-1,3-dioxolane of the formula (4)prepared by the above step (B-2) under an atmosphere of hydrogen in asolvent.

The examples of the solvents are esters such as ethyl acetate, butylacetate, etc., ethers, such as tetrahydrofuran, 1,4-dioxane,1,2-dimethoxyethane, etc., ketones, such as acetone, methyl ethylketone, methyl isobutyl ketone, etc., alcohols such as methanol,ethanol, propanol, butanol, etc., water and a mixture of these solvents.

The catalysts are not limited as far as catalysts used in this field,but preferable ones are metal catalysts such as palladium, platinum,etc., and palladium is more preferable in view of the yield and economy.Especially about 5-10% palladium-carbon powder is better. The amount ofthe catalyst is preferably 0.5 to 50 weight percent per4-alkoxymethyl-1,3-dioxolane. The reaction is usually carried out atroom temperature under the atmosphere.

Thus obtained 1,3-dioxolane-4-methanol compound is prepared in goodyield and high purity by usual purification methods, such asdistillation in vacuo.

In case of using an optically active 3-halogeno-1,2-propanediol as astarting material, there is obtained an optically active1,3-dioxolane-4-methanol compound. A 3-halogeno-1,2-propanediol withhigh optical purity (98% or more than 98%) is obtainable by methodsdescribed in Japanese Patent Publication B No. 4-73998, and No. 4-73999which were filed by the present applicant.

According to the present invention, by using a(R)-3-halogeno-1,2-propanediol, there is obtained a(S)-1,3-dioxolane-4-methanol compound. A R-form compound is prepared inthe same way. By using a 3-halogeno-1,2-propanediol with highly opticalpurity, there is obtained a 1,3-dioxolane-4-methanol compound withhighly optical purity without marked racemization on the reaction.

The present invention is explained by the following examples, but it isnot limited to these examples.

Examples 1 to 5, 7 and 6 are cases in variation of the halogen atoms(examples 1-5, 7: Cl, example 6: Br). Examples 1, 3, 5, 6, 2 and 4 arecases in variation of the carboxylates (example 1, 3, 5, 6: sodiumbenzoate, example 2, 4: sodium acetate). Examples 3, 4, 5 and 7 arecases used optically active 3-halogeno-1,2propanediols startingmaterial. Example 1 and 5 are cases of a reaction being carried out withor without a reaction promoter. Example 7 is a case of using an metalsalt of an alcohol.

EXAMPLE 1

p-Toluenesulfonic acid (1.79 g) was added to a mixture of3-chloro-1,2-propanediol (104.49 g, 0.945 mol) and acetone (1500 ml) andthe resulting mixture was stirred for 12 hours at 25° C. Aftercompletion of the reaction, acetone was removed in vacuo and the crudeproduct was distilled to give 128.01 g of4-chloromethyl-2,2-dimethyl-1,3-dioxolane (yield 89%, b.p. 45° C. at 5mmHg).

Then, sodium bromide (43.01 g, 0.42 mol) and sodium benzoate (60.24 g,0.42 mol) were added to a mixture of the above4-chloromethyl-2,2-dimethyl-1,3-dioxolane (60.02 g, 0.39 mol) andN,N-dimethylformamide (600 ml) and the resulting mixture was stirred for15 hours at 150° C. After cooling the salt was filtered off andN,N-dimethylformamide was removed in vacuo and water was added to theresidue and extracted with toluene. The extract was washed withsaturated brine, dried over anhydrous sodium sulfate and condensed invacuo to give crude 4-benzoyloxymethyl-2,2-dimethyl-1,3-dioxolane (yield90%).

Then sodium carbonate (32.22 g, 0.304 mol) was added to a mixture of thecrude 4-benzoyloxymethyl-2,2-dimethyl-1,3-dioxolane (48.06 g, 0.203 mol)and water (100 ml) resulting mixture was stirred for 8 hours at 100° C.After cooling the reaction mixture was extracted with methylenechloride. The extract was washed with saturated brine, dried overanhydrous sodium sulfate and condensed in vacuo. The crude product wasdistilled to give 22.03 g of 2,2-dimethyl-1,3-dioxolane-4-methanol(yield 82%, b.p. 72° C. at 8 mmHg).

EXAMPLE 2

To a mixture of 4-chloromethyl-2,2-dimethyl-1,3-dioxolane (51.60 g,0.343 mol) prepared by Example 1 and N,N-dimethylformamide (400 ml),sodium bromide (37.04 g, 0.36 mol) and sodium acetate (29.53 g, 0.36mol) were added and the resulting mixture was stirred for 15 hours at150° C. After cooling, the salt was filtered off andN,N-dimethylformamide was removed in vacuo. Water was added to theresidue and it was extracted with toluene and the extract was washedwith saturated brine, dried over anhydrous sodium sulfate and condensedin vacuo. The crude product was distilled to give 38.24 g of4-acetoxymethyl-2,2-dimethyl-1,3-dioxolane (yield 64%, b.p. 81° C. at 12mmHg).

Then sodium carbonate (40.63 g, 0.294 mol) was added to a mixture of4-acetoxymethyl-2,2-dimethyl-1,3-dioxolane (34.18 g, 0.196 mol) andmethanol (200 ml) and the resulting mixture was stirred for 8 hours at25° C. After completion of the reaction the salt was filtered off andthe filtrate was condensed in vacuo and water was added to the residueand extracted with methylene chloride. The extract was washed withsaturated brine, dried over anhydrous sodium sulfate and condensed invacuo. The crude product was distilled to give 23.12 g of2,2-dimethyl-1,3-dioxolane-4-methanol (yield 89%, b.p. 72° C. at 8mmHg).

EXAMPLE 3

p-Toluenesulfonic acid (0.86 g) was added to a mixture of(R)-3-chloro-1,2-propanediol (50.13 g, 0.454 mol, optical purity 98.7%e.e.) and acetone (660 ml) and the resulting mixture was stirred for 12hours at 25C. After completion of the reaction, acetone was removed invacuo and the crude product was distilled to give 58.11 g of(R)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane (yield 85%, b.p. 63° C. at25 mmHg).

Then, sodium bromide (24.70 g, 0.24 mol) and sodium benzoate (34.58 g,0.42 mol) were added to a mixture of(R)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane (36.48 g, 0.24 mol) andN,N-dimethylformamide (150 ml) and the resulting mixture was stirred for15 hours at 150° C. After cooling the salt was filtered off andN,N-dimethylformamide was removed in vacuo and water was added to theresidue and extracted with toluene. The extract was washed withsaturated brine, dried over anhydrous sodium sulfate and condensed invacuo to give 49.34 g ofcrude(R)-4-benzoyloxymethyl-2,2-dimethyl-1,3-dioxolane (yield 87%).

Then sodium carbonate (24.80 g, 0.234 mol) was added to a mixture of thecrude 4-benzoyloxymethyl-2,2-dimethyl-1,3-dioxolane (36.95 g, 0.156 mol)and water (80 ml) and resulting mixture was stirred for 8 hours at 100°C. After cooling the reaction mixture was extracted with methylenechloride. The extract was washed with saturated brine, dried overanhydrous sodium sulfate and condensed in vacuo. The crude product wasdistilled to give 15.67 g of (S)-2,2-dimethyl-1,3-dioxolane-4-methanol(yield 76%, b.p. 72° C. at 8 mmHg, optical purity 98.6% e.e., specificrotation [α]_(D) ²⁰ +11.1°(c=1,MeOH)).

EXAMPLE 4

Sodium bromide (57.93 g, 0.563 mol) and sodium acetate (46.18 g, 0.563mol) were added to a mixture of(R)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane (84.76 g, 0.563 mol)prepared by the same manner as Example 3 and N,N-dimethylformamide (800ml) and the resulting mixture was stirred for 15 hours at 150° C. Aftercooling the salt was filtered off and N,N-dimethylformamide was removedin vacuo and water was added to the residue and extracted with toluene.The extract was washed with saturated brine, dried over anhydrous sodiumsulfate and condensed in vacuo. The crude product was distilled to give60.81 g of (R)-4-acetoxymethyl-2,2-dimethyl-1,3-dioxolane (yield 62%,b.p. 78° C. at 10 mmHg).

Then potassium carbonate (66.96 g, 0.485 mol) was added to a mixture of(R)-4-acetoxymethyl-2,2-dimethyl-1,3-dioxolane (56.32 g, 0.323 mol) andmethanol (400 ml) and resulting mixture was stirred for 8 hours at 25°C. After completion of the reaction the salt was filtered off and thefiltrate was condensed in vacuo. Water was added to the residue and themixture was extracted with methylene chloride. The extract was washedwith saturated brine, dried over anhydrous sodium sulfate and condensedin vacuo. The crude product was distilled to give 38.27 g of(S)-2,2-dimethyl-1,3-dioxolane-4-methanol (yield 87%, b.p. 65° C. at 3mmHg, optical purity 97.5% e.e., specific rotation [α]_(D) ²⁰⁺10.87°(c=1,MeOH)).

EXAMPLE 5

Sodium benzoate (40.64 g, 0.282 mol) was added to a mixture of(R)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane (42.38 g, 0.282 mol)prepared by the same manner as example 3 and N,N-dimethylformamide (400ml) and the resulting mixture was stirred for 3 days at 150° C. Aftercooling the salt was filtered off and N,N-dimethylformamide was removedin vacuo and water was added to the residue and extracted with toluene.The extract was washed with saturated brine, dried over anhydrous sodiumsulfate and condensed in vacuo to give 58.63 g of crude(R)-4-benzoyloxymethyl-2,2-dimethyl-1,3-dioxolane (yield 88%).

Then sodium carbonate (39.43 g, 0.372 mol) was added to a mixture of thecrude (R)-4-benzoyloxymethyl-2,2-dimethyl-1,3-dioxolane (58.63 g, 0.248mol) and water (130 ml resulting mixture was stirred for 8 hours at 100°C. After cooling the reaction mixture was extracted with methylenechloride. The extract was washed with saturated brine, dried overanhydrous sodium sulfate and condensed in vacuo. The crude product wasdistilled to give 21.96 g of (S)-2,2-dimethyl-1,3-dioxolane-4-methanol(yield 67%, b.p. 65° C. at 3 mmHg, optical purity 97.3 % e.e., specificrotation [α]_(D) ²⁰ +10.84°(c=1,MeOH)

EXAMPLE 6

p-Toluenesulfonic acid (0.938 g) was added to a mixture of3-bromo-1,2-propanediol (76.34 g, 0.493 mol) and acetone (720 ml) andthe resulting mixture was stirred for 10 hours at 25° C. Aftercompletion of the reaction, acetone was removed in vacuo and theresidues was distilled to give 78.81 g of4-chloromethyl-2,2-dimethyl-1,3-dioxolane (yield 82%, b.p. 67° C. at 15mmHg)

Then, sodium benzoate (50.44 g, 0.35 mol) were added to a mixture of4-bromomethyl-2,2-dimethyl-1,3-dioxolane (58.52 g, 0.3 mol) andN,N-dimethylformamide (500 ml) and the resulting mixture was stirred for15 hours at 150° C. After cooling the salt was filtered andN,N-dimethylformamide was removed in vacuo and water was added to theresidue and extracted with toluene. The extract was washed withsaturated brine, dried over anhydrous sodium sulfate and condensed invacuo to give 64.5 g of crude4-benzoyloxymethyl-2,2-dimethyl-1,3-dioxolane (yield 91%).

Sodium carbonate (16.53 g, 0.156 mol) was added to a mixture of thecrude 4-benzoyloxymethyl-2,2-dimethyl-1,3-dioxolane (24.63 g, 0.104 mol)and water (50 ml) and resulting mixture was stirred for 8 hours at 100°C. After cooling the mixture was extracted with methylene chloride. Theextract was washed with saturated brine, dried over anhydrous sodiumsulfate and condensed in vacuo. The residue was distilled to give 10.86g of 2,2-dimethyl-1,3-dioxolane-4-methanol (yield 79%, b.p. 68° C. at 6mmHg).

EXAMPLE 7

Benzyl alcohol (32.90 g, 0.155 mol) was dropped under ice cooling in asuspension of 60% sodium hydride (5.88 g, 0.155 mol) and DMF (150 ml).After emission of hydrogen gas, sodium bromide (9.67 g, 0.094 mol) wasadded thereto. A DMF solution (15 ml) of(R)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane (11.747 g, 0.078 mol)prepared by the same manner as Example 3 was dropped in it. Thetemperature was raised to 120° C. and the mixture was stirred for 15hours. After completion of the reaction the reaction mixture was cooledon ice bath and neutralized with 6% hydrochloric acid. The solution wasextracted with ethyl acetate. The organic layer was washed with waterand with saturated brine, dried over anhydrous sodium sulfate andcondensed in vacuo. The crude product was distilled to give 9.627 g of(S)-4-benzyloxymethyl-2,2-dimethyl-1,3-dioxolane (yield 54%, b.p. 112°C. at 0.3 mmHg).

10% Palladium-carbon (2.63 g) was added to(S)-4-benzyloxymethyl-2,2-dimethyl-1,3-dioxolane (9.267 g, 41.69 mmol)in ethanol (250 ml) and the mixture was stirred for 3 hours at 25° C.under an atmosphere of hydrogen. After the reaction was over,palladium-carbon was filtered off and the solvent was condensed invacuo. The crude product was distilled to give 4.68 g of(S)-2,2-dimethyl-1,3-dioxolane-4-methanol (yield 85%, b.p. 65° C. at 3mmHg, optical purity 97.5% e.e., specific rotation [α]_(D) ²⁰⁺ 10.84°(c=1,MeOH)).

According to the present invention, 1,3-dioxolane-4-methanol compoundsare simply and economically prepared without expense reagents. A racemicor optically active compound of 1,3-dioxolane-4-methanol compounds is,if desired, prepared with high purity and in good yield.

What is claimed is:
 1. A process for preparing a1,3-dioxolane-4-methanol compound of the formula ##STR7## wherein R¹ andR² are the same or different and are hydrogen atom, alkyl having 1 to 4carbon atoms or phenyl, and R¹ and R² may form a cycloalkyl ring having3 to 6 carbon atoms with the adjacent carbon atoms,which ischaracterized in acetalizing a 3-halogeno-1,2-propanediol of the formula##STR8## wherein X is a halogen atom, with an acetalizing agent in thepresence of an acid catalyst to prepare a 4-halogenomethyl-1,3-dioxolaneof the formula ##STR9## wherein R¹, R² and X are as defined above, andreacting it with an alkali metal salt or alkaline earth metal salt of analcohol of the formula (3)

    ROH                                                        (3)

wherein R is aralkyl or allyl, to prepare a compound of the formula##STR10## wherein R, R¹ and R² are as defined above, and subjecting itto hydrogenolysis in the presence of a reductive catalyst.
 2. Theprocess for preparing a 1,3-dioxolane-4-methanol compound claimed inclaim 1, wherein a halogen atom in the formula (1) and (2) is chlorineatom or bromine atom.
 3. The process for preparing a1,3-dioxolane-4-methanol compound claimed in claim 1, wherein the acidcatalyst is p-toluenesulfonic acid, pyridinium p-toluenesulfonate,camphorsulfonic acid or trifluoroborate.
 4. The process for preparing a1,3-dioxolane-4-methanol compound claimed in claim 1, wherein theacetalizing agent is a compound selected from ketones mentioned below,aldehydes mentioned below, dialkoxyacetals of ketones mentioned belowand enol ethers of ketones mentioned below;Ketones: acetone, diethylketone, benzophenone, cyclohexanone, Aldehyde: formaldehyde,acetoaldehyde, benzaldehyde Dialkoxyacetals of ketones:2,2-dimethoxypropane, 2,2-dimethoxypentane, Enol ethers of ketones:2-methoxypropene.
 5. The process for preparing a1,3-dioxolane-4-methanol compound claimed in claim 4, wherein theacetalizing agent is a compound selected from acetone,2,2-dimethoxypropane and 2-methoxypropene.
 6. The process for preparinga 1,3-dioxolane-4-methanol compound claimed in claim 1, wherein thealkali metal salt or alkaline earth metal salt of an alcohol of theformula (3) is an alkali metal salt or alkaline earth metal salt ofbenzyl alcohol or allyl alcohol.
 7. The process for preparing a1,3-dioxolane-4-methanol compound claimed in claim 1, which ischaracterized in reacting a 4-halogenomethyl-1,3-dioxolane with analkali metal salt or alkaline earth metal salt of an alcohol in thepresence of a reaction promoter.
 8. The process for preparing a1,3-dioxolane-4-methanol compound claimed in claim 1, wherein thereduction catalyst is a palladium catalyst.
 9. The process for preparinga 1,3-dioxolane-4-methanol compound claimed in claim 1, which ischaracterized in preparing a 1,3-dioxolane-4-methanol of the formula (5)in an optically active form from a 3-halogeno-1,2-propanediol of theformula (1) in an optically active form.
 10. A process for preparing a1,3-dioxolane-4-methanol compound of the formula ##STR11## wherein R¹and R² are the same or different and are a hydrogen atom, alkyl having 1to 4 carbon atoms or phenyl, and R¹ and R² may form a cycloalkyl ringhaving 3 to 6 carbon atoms with the adjacent carbon,which ischaracterized in reacting a 4-halogenomethyl-1,3-dioxolane of theformula ##STR12## wherein R¹ and R² are the same as defined above and Xis a halogen atom, with an alkali metal salt or alkaline earth metalsalt of a carboxylic acid or an alcohol of the formula

    ROH                                                        (3)

wherein R is acyl, aralkyl or allyl, in the presence of a reactionpromoter to prepare a compound of the formula ##STR13## wherein R, R¹and R² are as defined above, and when R is acyl in the formula (4),subjecting it to hydrolysis, and when R is aralkyl or allyl in theformula (4) subjecting it to hydrogenolysis in the presence of areductive catalyst.
 11. The process for preparing a1,3-dioxolane-4-methanol compound claimed in claim 10, wherein thereaction promoter is a compound selected from alkali metal bromides andalkali metal iodides.
 12. The process for preparing a1,3-dioxolane-4-methanol compound claimed in claim 11, wherein thealkali metal bromide or alkali metal iodide is a compound selected fromsodium bromide, potassium bromide, sodium iodide and potassium iodide.13. The process for preparing a 1,3-dioxolane-4-methanol compoundclaimed in claim 10, wherein the alkali metal salt or alkaline earthmetal salt of an alcohol of the formula (3) is an alkali metal salt oralkaline earth metal salt of benzyl alcohol or allyl alcohol.
 14. Theprocess for preparing a 1,3-dioxolane-4-methanol compound claimed inclaim 10, wherein the reduction catalyst is a palladium catalyst. 15.The process for preparing a 1,3-dioxolane-4-methanol compound claimed inclaim 10, which is characterized in preparing a 1,3-dioxolane-4-methanolof the formula (5) in an optically active form from a3-halogenomethyl-1,3-dioxolane of the formula (2) in an optically activeform.